Materials and methods for the delivery of therapeutic nucleic acids to tissues

Abstract

The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.

What is claimed is: 
     
       1. A method of modulating beta cell proliferation comprising contacting the beta cell with a construct comprising an aptamer conjugated to a therapeutic RNA in an amount effective to modulate proliferation of the beta cell, wherein the therapeutic RNA is a siRNA or a saRNA, and wherein the aptamer is specific for clusterin (SEQ ID NO: 414) expressed on islets of Langerhans or “Transmembrane emp24 domain-containing protein 6” (TMED6, Genbank Accession No. NM144676.1) expressed on islets of Langerhans. 
     
     
       2. The method of  claim 1 , wherein the aptamer comprises the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259. 
     
     
       3. A method for inhibiting tissue graft apoptosis in a subject in need thereof comprising contacting the tissue graft with a construct comprising an aptamer conjugated to a therapeutic RNA, in an amount effective to inhibit apoptosis of the tissue graft, wherein the therapeutic RNA is a siRNA or a saRNA, and wherein the aptamer is specific for clusterin (SEQ ID NO: 414) expressed on islets of Langerhans or “Transmembrane emp24 domain-containing protein 6” (TMED6, NM144676.1) expressed on islets of Langerhans. 
     
     
       4. The method of  claim 3 , wherein the aptamer comprises the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259. 
     
     
       5. A method for protecting a beta cell from T-cell mediated cytotoxicity of the beta cell comprising contacting the beta cell with a construct comprising an aptamer conjugated to a therapeutic RNA, in an amount effective to inhibit T cell mediated cytotoxicity of the beta cell, wherein the therapeutic RNA is a siRNA or a saRNA, and wherein the aptamer is specific for clusterin (SEQ ID NO: 414) expressed on islets of Langerhans or “Transmembrane emp24 domain-containing protein 6” (TMED6, NM144676.1) expressed on islets of Langerhans. 
     
     
       6. The method of  claim 5 , wherein the aptamer comprises the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259. 
     
     
       7. A method for treating diabetes in a subject in need thereof comprising administering to the subject a construct comprising an aptamer conjugated to a therapeutic RNA, wherein the therapeutic RNA is a siRNA or a saRNA, and wherein the aptamer is specific for clusterin (SEQ ID NO: 414) expressed on islets of Langerhans or “Transmembrane emp24 domain-containing protein 6” (TMED6, NM144676.1) expressed on islets of Langerhans. 
     
     
       8. The method of  claim 7 , wherein the aptamer comprises the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259. 
     
     
       9. A method of delivering a therapeutic RNA to islets of Langerhans in a subject comprising administering construct comprising an aptamer conjugated to a therapeutic RNA to the subject, wherein the therapeutic RNA is a siRNA or a saRNA, and wherein the aptamer is specific for clusterin (SEQ ID NO: 414) expressed on islets of Langerhans or “Transmembrane emp24 domain-containing protein 6” (TMED6, NM144676.1) expressed on islets of Langerhans. 
     
     
       10. The method of  claim 9 , wherein the aptamer comprises the nucleotide sequence set forth in SEQ ID NO: 264 or SEQ ID NO: 259.